PROJECT SUMMARY (OVERALL) The overarching purpose of the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (RFK IDDRC) is to improve the lives of children with intellectual and developmental disabilities (IDD). Fifty years of distinguished progress in basic, translational and clinical research as one of NICHD's flagship IDDRCs, coupled with important recent faculty recruitments and an historic merger between the Albert Einstein College of Medicine and its University-Affiliated Hospital, Montefiore Medical Center, offer a solid platform for continuing excellence in our commitment to IDD research. The Center's 4 highly integrated and complemen- tary scientific Cores consist of: 1) our clinical translational core known as the Human Clinical Phenotyping (Core B, HCP), which serves to facilitate both access to and characterization of participants for IDD relevant research; 2) a Neurogenomics facility (Core C, NGEN) that provides cutting edge epigenetic and genomic processing and analyses on both human and animal tissues; 3) a Neural Cell Engineering and Imaging facility (Core D, NCEI) that provides state-of-the-art approaches to brain cell manipulation and visual-ization; and 4) an Animal Phenotyping facility (Core E, AP) for evaluation of animal behavior, metabolism, imaging and brain function in a manner with strong parallels to approaches taken in patients accessed through HCP. Each of our scientific Cores is carefully overseen and monitored by the Administrative Core (Core A, ADM), which also serves as the head ganglion of the entire IDDRC in its outreach programs to the Einstein/ Montefiore community as well as nationally. Each scientific Core is tightly connected to our selected Research Project which brings together a multidisciplinary team of investigators focused on intellectual disability in 22q11.2 Deletion Syndrome (22q11.2DS). A central function of the RFK IDDRC is to promote the substantive links between Einstein research laboratories and clinics at the Children's Evaluation and Rehabilitation Center (CERC) Children's and the Hospital at Montefiore (CHAM). Together, this set of Cores and our research project form a dynamic network of IDD-focused programs and practices that interlink 19 different academic departments and 20-plus IDD-relevant clinics at Einstein and Montefiore. The latter include 22q11.2DS, Rett and Williams syndromes, tuberous sclerosis, neurofibromatosis, West syndrome and infantile spasms, autism spectrum disorders, and a wide range of lysosomal diseases. New initiatives being set in motion involve outcome assessments of premature birth in terms of IDD and newborn screening (NBS) and critical genotype/ phenotype issues in conditions of high relevance to such NBS programs in New York State (Krabbe disease and adrenoleukodystrophy). Strong outreach programs driven by our ADM core help spread the word about IDD research. Such efforts over the past 5 years have positioned the RFK IDDRC in a substantive leadership role in coupling research and clinical strategic goals across the newly merged Einstein-Montefiore community, and will play an essential role in promotion of new clinical-research partnerships going forward.